Torsten Johnsson

An outbreak of aseptic meningitis with a rubella-like rash probably caused by ECHO virus type 4.

An outbreak of aseptic meningitis in association with ECHO-virus type 9 is described. This virus was isolated in 83% from stool specimens and in 47% from spinal fluids. There was a significant rise in homotypic neutralizing and CF antibody titer in the majority of the cases. As regards CF antibodies there was also a heterotypic response against ECHO-6 as well as a heterotypic response in sera from ECHO-6 and Coxsackie B 4 excretors against ECHO-9. A rubella-like exanthem was seen in about two thirds of the cases and in half of the patients there was a diphasic course. It seems probable that ECHO-virus type 9 can cause transient paralysis in man.

Studies on the etiology of epidemic pleurodynia (Bornholm disease). I. Clinical and virological observations.

The clinical picture in 28 patients treated for pleurodynia or suspected pleurodynia is briefly described. The incidence of recurrences, dry pleuritis and meningitis was high. Examination of spinal fluid, throat samples and stool specimens were carried out in 20 cases. In 7 of these strains of Coxsackie virus were isolated. Stools were positive in all 7 cases, throat swabs in 2 and spinal fluid in one case. Neutralizing antibodies against the strains isolated were present in convalescent sera in all cases. A certain evidence is presented to show that the virus found was of etiological importance.

A histopathological study of Coxsackie virus infections in mice.

The authors have studied the histopathological changes caused in mice by 35 Coxsackie virus strains, 12 A strains representing the immunological types A 1–A 10 and 23 B strains representing types B 2–B 4 according toDalldorf. Lesions in the 125 mice examined corresponded to the immunological typing and agreed, with a few divergences as regards myopathy and lesions in the internal organs, withDalldorfs classification of Coxsackie virus in subgroups A and B.

Studies of an epidemic of aseptic meningitis associated with Coxsackie and ECHO viruses. I. Virological observations.

An epidemic of aseptic meningitis was studied. Results of virus isolations and typing in two different types of tissue cultures, human embryonic lung cultures and cultures of trypsinized monkey kidney, and in baby mice indicated that the epidemic was mainly caused by ECHO virus type 6. This virus was prevalent in 57% of the cases. Coxsackie viruses were found in 13% and poliomyelitis virus type 3 in one %. In total, virus was recovered in 73%.

Family infections by Coxsackie viruses

With hospitalized cases of aseptic meningitis as a point of departure the author conducted a systematic study of the familial occurrence of Goxsackie virus infections. A virological, serological and clinical analysis was made of eight such families, where Coxsackie virus of the same immunological type was recovered from 2 to 3 members of the same family. In three families Coxsackie virus subgroup A and in five families subgroup B was found. In two patients the virus was found 3 and 9 days, respectively, prior to the onset of illness. Neutralizing antibodies to the respective types occurred in high titers in the majority of the household members, and in a number of cases a rise in titer during the acute phase was demonstrable. The only persons lacking antibodies were a couple of adults who had not been ill. Inapparent infections were demonstrated either through the finding of virus or through a rise in antibody titer during the period under review. Of those showing serological or virological evidence of infection 80 per cent were taken ill. Diagnoses varied from aseptic meningitis to pleurodynia, myalgia and minor illness. Infections by Coxsackie virus subgroup A appeared milder than those by subgroup B. Most cases of aseptic meningitis concerned children infected by type B 3 virus. Apart from pleocytosis, these children often had no direct symptoms suggestive of meningitis. Pleurodynia and myalgia, on the other hand, were more common in adults than in children. It appears likely that the infection was introduced into a household through one of the children, from whom it spread to the other members.

Studies on the etiology of Bornholm disease (epidemic pleurodynia)

An epidemic comprising 85 cases with varying symptoms but in obvious epidemiological connection is described. Observations were made at the time on 28 hospitalized patients and later in a field survey of the epidemic region. The clinical picture varied from typical pleurodynia and aseptic meningitis to minor illness. The age of the patient seemed to have a certain influence upon the type of the manifestations of infection, pleurodynia being more common in adults, aseptic meningitis in children. Coxsackie virus type B 3 was recovered from 7 of 20 patients examined. Antibodies to this type of virus were consistently found in high titers in the convalescence and a rise in titer during the acute stage was always demonstrable, provided the first blood sample was drawn before the fifth day of illness. The antibody content of a pool of 64 sera from persons having displayed symptoms, collected about three months after the subsidence of the epidemic was about a hundred times higher than those of a number of control groups examined at the same time. On the basis of this evidence it is concluded that the epidemic in spite of the variations in the clinical manifestations was etiologically homogeneous and caused by Coxsackie virus type B 3. Coxsackie virus type A 4 recovered from the throat of one patient was for several reasons considered to be without etiological significance for the epidemic in general.

The occurrence of Coxsackie virus in a hospital material of paralytic poliomyelitis, aseptic meningitis and a miscellaneous group of diseases

About two thirds of all cases in Stockholm of paralytic poliomyelitis and aseptic meningitis as well as a miscellaneous group of diseases were examined by the author for the presence of Coxsackie virus over a period of 4 years. In paralytic poliomyelitis Coxsackie virus was recovered in 0.9 per cent and in aseptic meningitis in 5.9 per cent; in 11.7 per cent in children up to 16 years of age and in 3.0 per cent in adults. In the miscellaneous group of diseases Coxsackie virus was recovered in 2.9 per cent. The percentage of Coxsackie positive cases of aseptic meningitis was fairly evenly distributed over the whole year. Statistical evidence was obtained to a certain degree of the etiological connection between Coxsackie virus and aseptic meningitis, especially concerning the connection of aseptic meningitis with Coxsackie virus subgroup B (5.8 per cent of children and 3 per cent of the adult cases). In the present material Coxsackie infections reached a peak in September at the same time as aseptic meningitis. In comparison it may be mentioned that mumps with meningitis reached its peak in the spring, when also a couple of cases were found of aseptic meningitis without mumps but with positive complement fixation. No such cases were encountered during the autumn.

Laboratory Infections with Coxsackie Viruses.

In a previously described outbreak of epidemic myalgia, in which Coxsackie virus (Dalldorfs type B 3) was recovered from about one third of the cases, there were a large number of patients with aseptic meningoencephalitis. Virus was recovered from the fluid of one of these patients. One of the strains isolated from the patient gave rise to infections of four laboratory workers, three with the clinical diagnosis of epidemic myalgia and one with meningo-encephalitis. In one of the patients with epidemic myalgia, who had a double infection with both A and B strains, there were vesicles in the posterior portion of the pharynx suggestive of herpangina. The same A-type (Dalldorfs type A 4) was isolated from a laboratory worker with symptoms of “minor illness”. In all cases a rise in neutralizing antibodies to the isolated strain was demonstrable. In experiments on two seriously malformed children orally infected with the above-mentioned B-strain the recurring fever typical of epidemic myalgia was with all probability reproduced. In another case only a sub-clinical infection was obtained. On the basis of these observations the author discusses the etiological rôle of Coxsackie virus in different syndromes.

Family infections with acute pericarditis and myocarditis by Coxsackie virus B 5

As we have heard in the excellent review given by Dr. J . Couvreur , the occurrence of myocarditis and pericarditis caused by Coxsackie B viruses in infants, older children and adults is fairly well established and there does not seem to be much to be added. Nevertheless, I will take the opportunity to shortly mention a few such cases in connection with the epidemic of Coxsackie B 5 we have had the last years in Sweden. The cases reported here do not deviate much from those described previously (Table 1). However, there are certain points of interest the authors want to underline. In the actual cases there is a familial occurrence of Coxsackie virus infections which we have found so common for infections with enteroviruses. Thus, there are not less than four cases of pericarditis in one of the families, as you can see in Table 1. The pleomorphism in the c]inical picture is also striking. As in previous family studies the infection in the family of the five members seems to have been introduced by the youngest member of the family, the nine year old boy, the last to fall ill being the father. The isolation procedure for enteroviruses, in recent years in the State Bacteriological Laboratory, has been inoculation in monkey kidney tissue culture and in suckling mice. To a certain extent human embryonic lung and kidney has also been used. The results of attempted virus isolations from 2,028 specimens as far as Coxsackie B viruses are concerned are listed in Table 2. Of 61 Coxsackie B 5 viruses isolated almost all could be isolated in monkey kidney tissue culture, while 30 % could be isolated in suckling mice. Two percent was isolated only in suckling mice. About half of the positive specimens was also tested in human embryonic kidney

A Non-Typable Cytopathic Agent as the Probable Cause of a Family Outbreak of Aseptic Meningitis.

In a familial infection of 4 cases of aseptic meningitis a cytopathogenic agent was isolated in tissue culture from the feces specimen of one of the cases. This cytopathogenic agent was neither serologically indentical with poliomyelitis virus types 1, 2 or 3, nor with Coxsackie virus types A 1–A 10 or B 1–B 4. Serological tests indicated that the isolated virus was responsible for 3 of the 4 cases. The clinical picture did not differ from that of aseptic meningitis caused by poliomyelitis or Coxsackie viruses.